Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus
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SYSTEMATIC REVIEW
Systematic Review: Monoclonal Antibody‑Induced Subacute Cutaneous Lupus Erythematosus Chrissy Bolton1,2,11 · Yifan Chen2 · Rachel Hawthorne3 · Ianthe R. M. Schepel2 · Elinor Harriss4 · Silke C. Hofmann5 · Spencer Ellis6 · Alexander Clarke7 · Helena Wace8 · Blanca Martin9 · Joel Smith10
© The Author(s) 2020
Abstract Background Subacute cutaneous lupus erythematosus (S(CLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. Methods We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs. Results From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not. Conclusion We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.
1 Introduction In an era of genomic medicine, the clear distinction of disease phenotypes is as critical as ever [1]. Integrated network analyses of—omics signatures are driving molecular disease classification that transcends organ-specific phenotypes [2]. However, a reductionist approach to disease classification retains its utility in the clinical setting and facilitates research [3]. Precise clinical phenotyping and confident diagnoses guide the initial therapeutic approach, provide an access key for interrogating large-scale datasets and make
Key Points Monoclonal antibody (mAb)-induced subacute cutaneous lupus erythematosus (SCLE) has been reported in 52 patients across a range of 17 mAbs. Adalimumab, denosumab and rituximab were estimated to have the greatest number of annual users. Checkpoint inhibitors and anti
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